title: Apoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy.
abstract: BACKGROUND
  Sonodynamic therapy (SDT) was developed as a localized ultrasound-activated cytotoxic therapy for cancer. The ability of SDT to destroy target tissues selectively is especially appealing for atherosclerotic plaque, in which selective accumulation of the sonosensitizer, protoporphyrin IX (PpIX), had been demonstrated. Here we investigate the effects of PpIX-mediated SDT on macrophages, which are the main culprit in progression of atherosclerosis.
  
  
  RESULTS
  Cultured THP-1 derived macrophages were incubated with PpIX. Fluorescence microscopy showed that the intracellular PpIX concentration increased with the concentration of PpIX in the incubation medium. MTT assay demonstrated that SDT with PpIX significantly decreased cell viability, and this effect increased with duration of ultrasound exposure and PpIX concentration. PpIX-mediated SDT induced both apoptosis and necrosis, and the maximum apoptosis to necrosis ratio was obtained after SDT with 20 μg/mL PpIX and five minutes of sonication. Production of intracellular singlet oxygen and secondary disruption of the cytoskeleton were also observed after SDT with PpIX.
  
  
  CONCLUSIONS
  PpIX-mediated SDT had apoptotic effects on THP-1 macrophages via generation of intracellular singlet oxygen and disruption of the cytoskeleton. PpIX-mediated SDT may be a potential treatment to attenuate progression of atherosclerotic plaque.
authors.affiliation: Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, PR China.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Guo
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Jiali
authors.initials: J
authors.lastname: Cheng
authors.forename: Haobo
authors.initials: H
authors.lastname: Xu
authors.forename: Juhua
authors.initials: J
authors.lastname: Dan
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lingli
authors.initials: L
authors.lastname: Meng
authors.forename: Wenwu
authors.initials: W
authors.lastname: Cao
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003599:Cytoskeleton / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000528:radiation effects; D009336:Necrosis; D011524:Protoporphyrins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000528:radiation effects; D026082:Singlet Oxygen / Q000378:metabolism; D013010:Sonication / Q000379:methods*; D018709:Statistics, Nonparametric; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000528:radiation effects
chemical_list: D011524:Protoporphyrins; D026082:Singlet Oxygen; C028025:protoporphyrin IX
keywords: atherosclerotic plaque; cytoskeleton; macrophage; protoporphyrin IX; singlet oxygen; sonodynamic therapy